The role of the pineal gland and its hormone, melatonin, has been difficult to define in humans, because the circulating levels of melatonin have been too low to measure. Recently, in collaboration with Dr. Sanford P. Markey of the LCS, we have developed a highly sensitive and specific gas chromatographic-mass spectrometric (GC-MS) assay which requires less than 1 ml of human plasma, CSF, or urine. Since the development of this assay, melatonin research has been extended into two broad areas: (1) investigation into the physiologic role of melatonin (circadian secretion, the effects of light, drugs, sleep, the menstrual cycle, and the seasons of the year) and pathologic roles (precocious puberty, delayed onset of puberty, infertility syndromes, hypothalamic, pituitary, adrenal, and thyroid diseases, hypertension, breast and ovarian malignancies, as well as affective disorders and schizophrenia); and (2) investigations of this hormone as a "marker" for (a) the "biologic clock", (b) beta-adrenergic receptor function.